1. Field of Invention
The present invention relates to a method and apparatus for generating an impedance spectrum which is characteristic of a sample of bodily matter in a resonant circuit.
2. Related Art
Numerous conditions may give rise to abnormalities in bodily tissue (eg disease, wounding, infection or cancer). In many cases, diagnosis may only be possible by taking a biopsy for ex vivo analysis. As well as being invasive, this method is inefficient and unable to provide rapid online data. In addition, the removal of a biopsy may cause significant discomfort to the subject
The electrical impedance spectrum exhibited by a sample or bodily matter is dependent upon its composition. Although bodily matter has previously been analysed by multi-frequency ac impedance measurements, the circuits used were not resonant. For example, it is known to use electrical impedance measurements to determine the status of a part of the body (see inter alia Dijkstra et al, Clinical Applications of Electrical Impedance Tomography, J Med. Eng. and Tech, 17, 3, 98xe2x80x9498).
The present invention is based on the recognition that the impedance spectrum of a sample of bodily matter which has been made part of a resonant electrical circuit is surprisingly sensitive to the characteristics of the sample of bodily matter and may be used to provide reliable and accurate detection of abnormalities in the sample (eg damaged or infected tissue). Moreover, the present invention is capable of providing information in real time whilst being substantially non-invasive.
Thus viewed from one aspect the present invention provides a method for generating an impedance spectrum which is characteristic of a sample of human or non-human bodily matter (eg tissue), said method comprising the steps of:
applying an electrical signal to the sample of bodily matter at each of a plurality of frequencies in a frequency range including a resonant frequency; and
measuring an impedance quantity at each of the plurality of frequencies in the frequency range whereby to generate the impedance spectrum.
Whilst not wishing to be bound by any theoretical consideration, it is nonetheless noted that an impedance quantity (Z+) reflects the response of a sample of bodily matter (eg tissue) to an alternating electric field stimulus and may be considered as a type of transfer function expressing the ratio of the output voltage to input current. This transfer function is related to the composition of the sample of bodily matter being tested
The impedance quantity may be considered equivalent to resistance (R) which is measured using direct current. However, in the frequency domain it is a complex number having both a real and an imaginary component expressed by:
Z+=R+jX
(where X is the reactance which is a function of frequency and j=xe2x88x921). The resonant frequency is that frequency at which reactance is zero and may be regarded as the frequency at which the inductive and capacitive contributions to the reactance cancel out.
Impedance quantities which may be measured in accordance with the invention include the reactance (X) and the phase angle (xcex8) which are by definition zero at the resonant frequency. A preferred impedance quantity is the dissipation factor (DF) defined as:
DF=R/X
DF is a measure of the energy dissipated in a circuit by the resistive heating relative to the energy stored in a circuit by capacitive and inductive mechanisms. DF reaches a maximum as X reaches zero (ie as the resonant frequency is reached)
In one embodiment of the invention, the electrical signal is a time varying electrical signal. Preferably, the time varying electrical signal is an alternating current (ac) signal.
The measurement of the impedance quantity may comprise a time to frequency domain transformation of the time varying electrical signal. The steps involved in such a measurement will be generally familiar to those skilled in the art (see for example Perturbation Signals for System Identification, ed K Godfrey, Prentice Hill, 1993, UK). The time varying electrical signal may be periodic and may comprise any suitable function or code eg a pseudo random binary sequence (PRBS), a Golay code, a Walsh function, a Huffman sequence or any other suitable coded sequence. Other suitable signals, codes or methodologies such as white Gaussian noise or wavelet analysis may be employed and will be generally familiar to those skilled in the art (see for example Signal Processing Methods for Audio Images and Telecommunications, ed P M Clarkson and H Stork, Academic Press, London, 1995).
The electrical signal may be applied by at least two electrodes. The electrodes may be in direct or indirect electrical contact With the sample of bodily matter. For example, an insulating layer may be placed over one or more of the electrodes so that the electrodes are in indirect electrical contact with the sample of bodily matter.
In a preferred embodiment of the method of the invention, the electrical signal may be applied by one or more microelectrodes of the type generally or specifically disclosed in WO-A-99/60392 (Farfield Sensors Limited) or specifically claimed therein.
Alternatively, the electrical signal may be applied via at least two windings. The windings may be in direct or indirect electrical contact with the sample of bodily matter.
A means for varying the frequency of the applied electrical signal may be used to apply the electrical signal at a plurality of frequencies in a range including the resonant frequency. For example, at least one inductor or one or more quartz crystal resonators may be used. Conveniently, the means for varying the frequency of the applied electrical signal ensures that the resonant frequency is below about 1 MHz. At such a resonant frequency, problems associated with instrumentation and digitisation are generally reduced.
In a preferred embodiment, the method of the invention comprises the step of comparing the impedance spectrum of an abnormal sample of bodily matter with the impedance spectrum of a normal (ie healthy) sample of bodily matter to deduce the relative characteristics of the normal and the abnormal sample. The term xe2x80x9cabnormal sample of bodily matterxe2x80x9d may include inter alia cancerous, scarred, infected or diseased tissue.
For example, the impedance spectra may be compared to deduce a shift in the resonant frequency or a difference in the magnitude of the impedance quantity at or near to the resonant frequency. In turn, the relative characteristics of the abnormal and normal sample of tissue may be deduced in a further step.
The method of the invention may be used to detect abnormalities in normal bodily tissue. For example, the method may be advantageously used to detect abnormalities in external bodily tissue including inter alia skin abnormalities, tooth decay, gum disease or cancerous growths. However the method may equally be used on interior bodily tissue to detect abnormalities such as bone abnormalities or cancerous tissue.
In a preferred embodiment, the method of the invention comprises the following steps:
applying a first electrical signal to a first sample of bodily matter at each of a plurality of frequencies in a first frequency range including a resonant frequency;
measuring an impedance quantity at each of the plurality of frequencies in the first frequency range whereby to generate an impedance spectrum of the first sample;
applying a second electrical signal to a second sample of bodily matter at each of a plurality of frequencies in a second frequency range including a resonant frequency;
measuring an impedance quantity at each of the plurality of frequencies in the second frequency range whereby to generate an impedance spectrum of the second sample;
comparing the impedance spectrum of the first sample and the impedance spectrum of the second sample; and
deducing the relative characteristics of the first and the second sample of bodily matter.
By way of example, the first sample may be a normal sample of bodily matter (eg healthy tissue) and the second sample may be an abnormal sample of bodily matter. The step of comparing may comprise calculating the shift in resonant frequency between the normal sample of bodily matter and the abnormal sample of bodily matter.
The sensitivity of the method of the invention is such that the shift in the resonant frequency between a sample of normal and a sample of abnormal bodily matter may be significant and may be a downward or an upward shift. For example, a downward shift in resonant frequency is typically characteristic of a sample of diseased skin vis a vis a sample of normal skin whilst an upward shift in resonant frequency is typically characteristic of a sample of scar tissue vis a vis a sample of normal skin. Typically the shifts are as significant as xe2x88x9290 kHz and +100 kHz respectively.
Alternatively, the step of comparing may comprise calculating a change in the magnitude of the impedance quantity at the resonant frequency. This is useful where the impedance quantity is the dissipation factor.
Viewed from a further aspect the present invention provides an apparatus for generating an impedance spectrum which is characteristic of a sample of human or non-human bodily matter (eg tissue), said apparatus comprising:
electrical signal applying means adapted to apply a time varying electrical signal to the sample of bodily matter at each of a plurality of frequencies in a frequency range including a resonant frequency; and
measuring means for measuring an impedance quantity characteristic of the sample of bodily matter at each of the plurality of frequencies in the frequency range whereby to generate the impedance spectrum.
In an embodiment of the apparatus of the invention, the electrical signal applying means is capable of applying an ac signal of variable frequency.
In an embodiment of the apparatus of the invention, the electrical signal applying means is capable of applying a time varying electrical signal which is periodic.
The electrical signal applying means may be adapted for use ex vivo or in vivo (externally or internally) as required. The electrical signal applying means may be capable of being positioned in direct or indirect electrical contact with the bodily matter.
The electrical signal applying means may comprise a means for varying tie frequency of the electrical signal to apply the electrical signal at a plurality of frequencies in a range including the resonant frequency. For example, the apparatus may further comprise at least one inductor or at least one quartz crystal resonator. Conveniently, the means for varying the frequency of the electrical signal is arranged so that the resonant frequency is below about 1 MHz. At such a resonant frequency, problems associated with instrumentation and digitisation are generally reduced.
The electrical signal applying means may comprise at least two electrodes. The electrodes may be capable of being positioned in direct or indirect electrical contact with the bodily matter. For example, one or more of the electrodes may comprise an outer insulating layer so that the electrodes are capable of being positioned in indirect electrical contact with the sample of bodily matter.
Numerous electrode materials, sizes and configurations are suitable (as desired) for the preferred embodiment. Generally, the configuration and material may be tailored to the end use. For example, planar electrodes may be used where the sample of bodily matter comprises the skin. Such planar electrodes may be rectangular or half ring configurations as desired. Multiple electrode arrangements may be used where desired. Modulation of the applied electrical field strength is possible to find the optimum working field strength or to provide additional information on the tissue sample.
In a preferred embodiment of the apparatus of the invention, the electrical signal applying means comprises one or more microelectrodes of the type generally or specifically disclosed in WO-A-99/60392 (Farfield Sensors Limited) or specifically claimed therein.
The electrical signal applying means may comprise at least two windings. The windings may be capable of being positioned in direct or indirect electrical contact with the bodily matter. For example, the windings may be potted in a casing of an inert material. This embodiment acts in a similar manner to a transformer ie wherein one winding is energised as a primary winding and drives a second winding which acts as a secondary winding. A current may be induced in the secondary winding with an efficiency which depends on the impedance of the medium between the primary and secondary windings.
In an embodiment of the invention, the electrical signal applying means comprises a probe adapted to be inserted into a bodily cavity and to enable measurement of the impedance spectrum characteristic of the surrounding tissue. The probe may be useful in internal use eg in the detection of cancer (eg cervical cancer). The probe may comprise one or more suitably shaped electrodes (eg needle electrodes) insertable into the bodily cavity.
In an embodiment of the apparatus of the invention, the measuring means may comprise an impedance analyser.
In an embodiment of the apparatus of the invention, the measuring means may be capable of performing a time to frequency domain transformation of the time varying electrical signal.
Viewed from a yet further aspect the present invention provides the use of an apparatus as hereinbefore defined for generating an impedance spectrum at each of a plurality of frequencies in a frequency range including a resonant frequency which is characteristic of a sample of human or non-human bodily matter. Preferably the sample is an exterior part of the human or non-human body (eg the skin).
Viewed from a yet still further aspect the present invention provides a kit of parts suitable for generating an impedance spectrum at each of a plurality of frequencies in a frequency range including a resonant frequency which is characteristic of a sample of human or non-human bodily matter, said kit comprising:
at least two electrodes for applying alternating current to the sample of bodily matter;
an inductor; and
an impedance analyser capable of measuring an impedance quantity at each of the plurality of frequencies in the frequency range including the resonant frequency whereby to generate the impedance spectrum.